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. 2018 Apr 14;15(1):108.
doi: 10.1186/s12974-018-1150-4.

Platelet-derived Growth Factor Predicts Prolonged Relapse-Free Period in Multiple Sclerosis

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Free PMC article

Platelet-derived Growth Factor Predicts Prolonged Relapse-Free Period in Multiple Sclerosis

Mario Stampanoni Bassi et al. J Neuroinflammation. .
Free PMC article

Abstract

Background: In the early phases of relapsing-remitting multiple sclerosis (RR-MS), a clear correlation between brain lesion load and clinical disability is often lacking, originating the so-called clinico-radiological paradox. Different factors may contribute to such discrepancy. In particular, synaptic plasticity may reduce the clinical expression of brain damage producing enduring enhancement of synaptic strength largely dependent on neurotrophin-induced protein synthesis. Cytokines released by the immune cells during acute inflammation can alter synaptic transmission and plasticity possibly influencing the clinical course of MS. In addition, immune cells may promote brain repair during the post-acute phases, by secreting different growth factors involved in neuronal and oligodendroglial cell survival. Platelet-derived growth factor (PDGF) is a neurotrophic factor that could be particularly involved in clinical recovery. Indeed, PDGF promotes long-term potentiation of synaptic activity in vitro and in MS and could therefore represent a key factor improving the clinical compensation of new brain lesions. The aim of the present study is to explore whether cerebrospinal fluid (CSF) PDGF concentrations at the time of diagnosis may influence the clinical course of RR-MS.

Methods: At the time of diagnosis, we measured in 100 consecutive early MS patients the CSF concentrations of PDGF, of the main pro- and anti-inflammatory cytokines, and of reliable markers of neuronal damage. Clinical and radiological parameters of disease activity were prospectively collected during follow-up.

Results: CSF PDGF levels were positively correlated with prolonged relapse-free survival. Radiological markers of disease activity, biochemical markers of neuronal damage, and clinical parameters of disease progression were instead not influenced by PDGF concentrations. Higher CSF PDGF levels were associated with an anti-inflammatory milieu within the central nervous system.

Conclusions: Our results suggest that PDGF could promote a more prolonged relapse-free period during the course of RR-MS, without influencing inflammation reactivation and inflammation-driven neuronal damage and likely enhancing adaptive plasticity.

Keywords: CIS; Cytokines; Neuroinflammation; PDGF; RR-multiple sclerosis.

Conflict of interest statement

Ethics approval and consent to participate

The study involving human subjects, according to the Declaration of Helsinki, was approved by the Ethics Committee of the University Hospital Tor Vergata, Rome. All patients gave their written informed consent to the study.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Influence of CSF PDGF levels on clinical and radiological disease activity. a The probability to not reach a clinical relapse, the RFS, according to the PDGF group. RFS was higher in both “medium PDGF” and “high PDGF” groups compared to patients with “not detected PDGF”. b The probability to not reach the first MRI progression during the observational period, the MRI progression-free survival in the three PDGF groups. No significant difference was found in the three PDGF groups
Fig. 2
Fig. 2
CSF PDGF levels and markers of neurodegeneration and axonal damage. The figure shows the correlations between CSF PDGF levels and the levels of amyloid-β 1–42 (a), tau protein (b), and NFL protein (c). To obtain a better graphical representation, all variables are depicted on logarithmic scale. Spearman rho correlations were calculated on the variables’ original scale. No significant correlation was found between CSF PDGF concentrations and the levels of markers of neurodegeneration and axonal damage. The p values showed were not adjusted by the Benjamini–Hochberg FDR controlling procedure

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References

    1. Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002;15:239–245. doi: 10.1097/00019052-200206000-00003. - DOI - PubMed
    1. Frohman EM, Racke MK, Raine CS. Multiple sclerosis—the plaque and its pathogenesis. N Engl J Med. 2006;354:942–955. doi: 10.1056/NEJMra052130. - DOI - PubMed
    1. Centonze D, Muzio L, Rossi S, Cavasinni F, De Chiara V, Bergami A, et al. Inflammation triggers synaptic alteration and degeneration in experimental autoimmune encephalomyelitis. J Neurosci. 2009;29:3442–3452. doi: 10.1523/JNEUROSCI.5804-08.2009. - DOI - PMC - PubMed
    1. Rossi S, Studer V, Motta C, De Chiara V, Barbieri F, Bernardi G, et al. Inflammation inhibits GABA transmission in multiple sclerosis. Mult Scler. 2012;18:1633–1635. doi: 10.1177/1352458512440207. - DOI - PubMed
    1. Mori F, Nisticò R, Mandolesi G, Piccinin S, Mango D, Kusayanagi H, et al. Interleukin-1βpromotes long-term potentiation in patients with multiple sclerosis. NeuroMolecular Med. 2014;16:38–51. doi: 10.1007/s12017-013-8249-7. - DOI - PubMed
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